Trained primarily as a clinician, Dr. Chi turned his focus towards clinical research in July 2003, when he joined the OB/GYN faculty at the University of Alabama at Birmingham (UAB). He moved to Lusaka, Zambia to participate in the university's expanding research activities in international health. Recognizing the project-focused nature of his current work, Dr. Chi is applying for this award in order to obtain more comprehensive training. The candidate has designed a structured curriculum to complement his research activities, one that includes grant writing seminars, research ethics courses, and formal coursework for a Masters-level degree in epidemiology. He has enlisted the help of U.S. and Zambia-based mentors, all with experience and success in training young scientists. With their guidance, Dr. Chi should have a productive start to his academic career in international women's health and the prevention of mother-to-child transmission of HIV (PMTCT), his primary interest. For the research component of this application, Dr. Chi addresses a pressing issue in PMTCT within sub-Saharan Africa. Since the demonstration of intrapartum nevirapine (NVP) as a cheap, simple, and effective means of reducing PMTCT, many national programs have incorporated the drug into their standard care. Though the public health benefits cannot be understated, widespread use of NVP in this fashion may come at a cost. Recent work shows NVP resistance may peak at two weeks postingestion, at a frequency as high as 75%. Though mutations generally fade to undetectable levels by 12 months using standard assays, there is growing concern that their one-time presence may predict reduced efficacy of NVP, or other non-nucleoside reverse transcriptase inhibitors (NNRTIs), in long-term HAART. It is clear that innovative approaches are needed to address this issue. Dr. Chi proposes a randomized trial to investigate what impact the addition of 2 drugs, zidovudine (ZDV) and lamivudine (3TC), to the standard maternal NVP regimen may have on NNRTI resistance post-delivery. 2 NVP-containing regimens will be tested. The first will consist of a single-dose, three drug combination tablets to be taken at the onset of labor. The second regimen will incorporate the same three-drug combination during labor, along with a 10-day, postpartum course of ZDV/3TC. The third group will utilize the standard NVP regimen as described by HIVNET-012 and serve as a control arm. All infants will receive 2 mg/kg of NVP syrup. The primary outcome will be the prevalence of HIV resistance mutations at two weeks postpartum. In order to detect a reduction from 75% to 45%, 70 participants will be recruited into each arm for a total of 210. Second outcomes include feasibility, frequency of 3TC resistance mutations, and infant HIV transmission at 6 weeks postpartum. Follow-up will continue out to one-year post-delivery.